1. Field of the Invention
The present disclosure relates to inhibition of Clostridium difficile. More particularly, the present disclosure relates to a novel use of Fe3-δO4 nanoparticle in inhibiting the spore germination of Clostridium difficile. 
2. Description of Related Art
Spore formation enables bacteria to survive harsh environment and nutrition deprivation, including resisting ultraviolet radiation, desiccation, high temperature, extreme freezing and chemical disinfectants. The spores can reactivate itself to the vegetative state when the environment becomes favorable. Therefore, the spore-forming pathogens present a challenge to clinical disease management and prevention, e.g., infection of Bacillus and Clostridium. Clostridium difficile, a pathogen associated with healthcare—relevant infections, particularly, C. difficile infection (CDI), is one of the major causes for antibiotic treatment related diarrhea, pseudomembranous colitis, abdominal pain, fever and death. Once CDI is found, only a few antibiotics are available to contain the disease. Furthermore, both the failure rate of first-line antibiotics and the relapse rate are high. As a consequence, the attributable mortality rate is 6.9% at 30 days after diagnosis and 16.7% at 1 year.
The spores of C. difficile are the major cause of CDI. Compared to oxygen sensitive vegetative bacteria, C. difficile spores may sustain harsh environment (such as the hospital surfaces) for up to several months. It is known that the normal flora in gut can suppress the growth of C. difficile and therefore may suppress CDI. However, CDI usually occurs in patients that are subjected to long-term use of antibiotics, and it is often initiated by the spores acquired from healthcare workers. As the spores enter the human digestive tract, they germinate upon being exposed to taurocholate or their derivatives and then colonized in the colon. The virulence of C. difficile dependents on the expression of tcdA encoding toxin A, an enterotoxin, and tcdB encoding toxin B, a cytotoxin, respectively. Both would cause intestinal inflammation and the neutrophils infiltration in the infected foci.
In view of the increasing incidence of CDI, which is becoming a major cause of healthcare-associated infection in the world, how to efficiently control or treat CDI becomes an urgent issue. A number of different antibiotics have been used for the treatment of CDI, including Metronidazole, Vancomycin, and Fidaxomicin. Although those antibiotics usually can slow or stop the symptom associated with CDI, they may also lead to the development of antibiotics-resistant strain of C. difficile. Besides, appearance of spores that are resistant to chemical agents further deteriorates the CDI clinical management. Some newly designed cholate derivatives exhibit promising effect against CDI; however they are still under pre-clinical study. Sodium hypochlorite, a standard disinfectant, exhibits outstanding antimicrobial activity, yet it also possesses unfavorable effects including corrosive property and irritation to tissues.
Due to the non-satisfactory therapeutic efficacy of the known typical treatments, various novel approaches are now being developed and attempt to solve this healthcare distress. Among these approaches, nanoparticles have attracted significant interests for their antibacterial properties acting through different mechanisms, including the generation of reactive oxygen species, disruption of cell membrane, release of toxic ions, and/or thio group-binding capacity. The known nanoparticles with the antibacterial property include Ag, ZnO, TiO2, and zero-valent iron nanoparticles. Nevertheless, most current anti-bacteria nanoparticles possess biocidal activity against vegetative cells, but not the sporicidal activity against spores.
In view of the foregoing, there exist a need in the related art to develop an effective and biocompatible spore control strategy so as to control the spore germination and to treat CDI.